Head and Neck Cancers
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Head and neck cancers are malignancies arising in the upper aerodigestive tract (this includes: lip, tongue, salivary glands, mouth, oropharynx, nasopharynx, hypopharynx, nasal cavity, and larynx). Laryngeal (voice-box) cancer is the most frequent type, accounting for about a quarter of head and neck cancers.

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Molecular Biology of Head and Neck Cancers
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Latest Research Publications

Head and Neck Cacer Resources (16 links)

Latest Research Publications

This list of publications is regularly updated (Source: PubMed).

Rivera G, Lugo-Vicente H
Thyroid cancer in children.
Bol Asoc Med P R. 2014; 106(3):48-54 [PubMed] Related Publications
Cancer of the thyroid gland in pediatric patients is rare and if left untreated spreads and become lethal. Thyroid nodules in pediatric patients are four times more likely being malignant than adult nodules. The incidence of thyroid cancer in children increases with age, sex, race and nodule size. Exposures to low level of head and neck irradiation at young age, cancer survivors, family history of thyroid cancer and iodine deficiency are specific risk factors to develop thyroid cancer. Thyroid cancer is subdivided into papillary, follicular and medullary thyroid cancer varying in histological characteristics. Children who present with thyroid nodules should undergo ultrasound and fine needle aspiration biopsy to evaluate malignant potential. If biopsy results are positive for malignancy best option is complete surgical resection of the thyroid gland with central lymph node dissection followed by radioactive iodine treatment. Surgeons need to take certain precaution to avoid postoperative complications like hypoparathyroidism or recurrent laryngeal nerve damage. Follow-up is essential in order to evaluate remission or recurrence. An excellent prognosis in pediatric patients is the result of such an aggressive approach that can be supported by the low complications rate and low recurrence rate following surgery.

Related: Thyroid Cancer

Alvarado M, Ramirez-Vick M, Lopez L, et al.
An uncommon presentation of follicular thyroid carcinoma: when chronic back pain should raise a flag.
Bol Asoc Med P R. 2014; 106(3):36-9 [PubMed] Related Publications
Follicular thyroid carcinoma is the second most common type of thyroid cancer, and its incidence has increased dramatically in recent years. Although it typically presents as a thyroid nodule, it can spread to distant sites via hematogenous dissemination. Bone metastasis is diagnosed clinically in 2%-13% of patients with differentiated thyroid cancer; nevertheless spinal cord compression complicating thyroid carcinoma is rare and only few cases has been reported in the literature. This case illustrates a strange case of a minimally invasive follicular carcinoma that showed an aggressive behavior, and thus the importance of considering metastatic thyroid carcinoma in the differential diagnosis of chronic back pain progressing to spinal cord compression carrying a severe morbidity.

Related: Thyroid Cancer

Tanaka T, Niwa Y, Tajika M, et al.
Prospective evaluation of a transnasal endoscopy utilizing flexible spectral imaging color enhancement (FICE) with the Valsalva maneuver for detecting pharyngeal and esophageal cancer.
Hepatogastroenterology. 2014; 61(134):1627-34 [PubMed] Related Publications
BACKGROUND/AIMS: This study evaluated the efficacy and safety of transnasal endoscopy (TNE) with flexible spectral imaging color enhancement (FICE) for detection of superficial cancer in the pharyngeal and esophageal regions for high-risk populations.
METHODOLOGY: Patients who previously had head and neck or esophageal squamous cell carcinoma were enrolled. Screening was conducted using TNE with conventional white-light endoscopy (WLE) followed by FICE chromoendoscopy. For observation of the pharyngeal region, the Valsalva maneuver was employed.
RESULTS: 99 patients were eligible. Six esophageal cancers were detected in four patients (4.0%). The sensitivity, specificity, and accuracy for the detection of cancer were 25.0% (95% CI, 3.4- 71.0), 97.8% (95% CI, 92.1-99.8), and 94.9 % (95% CI, 88.4-98.1), respectively for WLE; 100% (95% CI, 45.4%- 100%), 96.8% (95% CI, 90.7%-99.3%), and 96.9% (95% CI, 89.3%-99.1%), respectively for FICE chromoendoscopy. Pain in the nose and nasal hemorrhage were observed in 3 (3.0%) and 2 patients (2.0%), respectively. Following the Valsalva maneuver, endoscopic scores significantly increased from a mean of 1.1 (0.8-1.4) to 2.0 (1.3-2.6) (p<0.05).
CONCLUSIONS: TNE with the Valsalva maneuver is a promising screening method for the pharyngeal and esophageal regions. TNE with FICE chromoendoscopy for detecting pharyngeal and esophageal cancer was more sensitive than WLE.

Related: Cancer of the Esophagus Esophageal Cancer

Hagiwara K, Kochi M, Fujii M, et al.
Radiochemotherapy for esophageal squamous cell carcinoma in elderly patients.
Hepatogastroenterology. 2014; 61(134):1617-22 [PubMed] Related Publications
BACKGROUND/AIMS: The goal of this retrospective study was to investigate the efficacy and safety of curative radiochemotherapy (CRT) in elderly patients with esophageal squamous cell cancer (SCC).
METHODOLOGY: Between 1986 and 2011, 38 consecutive patients aged over 75 years with esophageal SCC were initially treated with a CRT regimen comprising radiation therapy at a dose of 60 Gy and two cycles of chemotherapy with 5-fluorouracil/cisplatin.
RESULTS: Fourteen patients were aged over 80 and 24 under 79 years. Complete treatment compliance was obtained in 30 (78.9%) of the patients. Chemotherapy was terminated and the dose of radiation reduced in 7 and 1 patients, respectively. The overall incidence of CRT-related complications was 86.8% (33 patients). Grade 3 leukocytopenia was observed in 6 (15.8%) patients, all of whom recovered promptly. A complete response was observed in 17 patients (44.7%). The overall 3-year survival rate was 32.0%.
CONCLUSIONS: Curative CRT is safe and may improve overall and progression-free 3-year survival rates in elderly patients aged more than 75 years with esophageal SCC.

Related: Cisplatin Cancer of the Esophagus Esophageal Cancer Fluorouracil

Kunisaki C, Makino H, Kimura J, et al.
Postoperative surveillance and prognostic factors in patients with esophageal cancer.
Hepatogastroenterology. 2014 Jul-Aug; 61(133):1262-73 [PubMed] Related Publications
BACKGROUND/AIMS: Here we investigated postoperative prognostic factors and surveillance in patients with esophageal cancer. METHODOLOGY Prognostic factors were evaluated at several different postoperative stages in 257 patients with curative (R0) esophagectomy. Cause of death and pattern of tumor recurrence were also analyzed.
RESULTS: There was a significant difference in the distribution of cause of death according to the time after surgery (p<0.001). The pattern of recurrence also differed according to the time after surgery, although this was not statistically significant. A Cox proportional regression hazard model for disease-specific survival revealed that Tumor-Node-Metastasis (TNM) stage was an independent prognostic factor only from the time of initial surgery until the third postoperative year, and no postoperative prognostic factors were detected after the fourth and fifth years. There were significant differences in disease-specific survival among pathological TNM stages between the time of initial surgery and postoperative year five, but not between stages I and II at postoperative years two, three, or four. There were no significant differences between the stages at postoperative year five. Relapse-free survival differed between stages II and III at postoperative year five, although the other results were similar to those for disease-specific survival.
CONCLUSIONS: Prognostic factors for esophageal cancer alter during the postoperative period. Although the pathological stage at the time of initial surgery has less prognostic power after 3 years, it remains important to monitor treatments for esophageal cancer continuously, as well as concomitant diseases and other malignancies.

Han Y, Zhao H, Xu H, et al.
Cure and prevention strategy for postoperative gastrointestinal fistula after esophageal and gastric cardiac cancer surgery.
Hepatogastroenterology. 2014 Jul-Aug; 61(133):1253-6 [PubMed] Related Publications
Gastrointestinal fistula is the most serious complication of esophageal and gastric cardiac cancer surgery. According to occurrence of organ, gastrointestinal fistula can be divided into anastomotic fistula, gastric fistula; According to occurrence site, fistula can be divided into cervical fistula, thoracic fistula; According to time of occurrence, can be divided into early, middle and late fistula. There are special types of fistula including ‘thoracic cavity’-stomach-bronchial fistula, ‘thoracic cavity’-stomach-aortic fistula. Early diagnosis needs familiarity with various types of clinical gastrointestinal fistulas. However, Prevention of gastrointestinal fistula is better than cure, including perioperative nutritional support, respiratory tract management, and acid suppression, positive treatment of complications, antibiotic prophylaxis, and gastrointestinal decompression and eating timing. Prevention can effectively reduce the incidence of postoperative gastrointestinal fistula. Collectively, early diagnosis and treatment, nutritional supports are key to reducing mortality of gastrointestinal fistula.

Related: Cancer of the Esophagus Esophageal Cancer Stomach Cancer Gastric Cancer

Navarro-Dourdil M, Charro-Calvillo M, Uribarrena-Amézaga R, Sebastián-Domingo JJ
Endoscopic follow-up and management of Barrett's esophagus in relation to its preneoplastic potential.
Hepatogastroenterology. 2014 Jul-Aug; 61(133):1241-5 [PubMed] Related Publications
Barrett's esophagus is an acquired clinical condition in which the squamous epithelium of the distal esophagus is replaced by a columnar epithelium. The diagnosis requires histological confirmation of specialized intestinal metaplasia, in which goblet cells must be present. Barrett's esophagus is a risk factor for the development of esophageal adenocarcinoma, a tumor with an incidence and mortality have increased alarmingly in recent years in the western world. It has been estimated that the annual incidence of cancer in patients with Barrett's esophagus has increased from 0.2-2%. Once diagnosed, Barrett's esophagus is estimated to have an annual neoplastic transformation rate of 0.5% per patient. The highlights of the endoscopic diagnosis and treatment are reviewed here, as well as the screening and monitoring of this process.

Related: Cancer of the Esophagus Esophageal Cancer

Lee T, Tanaka H, Ohira M, et al.
Intranodal cytokeratin particles is a predictive marker of efficacy for neoadjuvant therapies in patients with squamous cell carcinoma of the esophagus.
Hepatogastroenterology. 2014 Jul-Aug; 61(133):1235-40 [PubMed] Related Publications
BACKGROUND/AIMS: Lymph node metastasis is one of the most important prognostic factors in patients with esophageal squamous cell carcinoma (ESCC). Neoadjuvant treatment can reduce micrometastasis in lymph nodes to enable curative resection by down staging. The aim of this study was to evaluate the histological effect of neoadjuvant therapy on lymph node metastasis of ESCC by performing immunohistochemistry for cytokeratin staining.
METHODOLOGY: A total of 3061 lymph nodes were examined from 62 patients who received neoadjuvant treatment followed by esophagectomy with lymphadenectomy.
RESULTS: We observed positive staining for cytokeratin in 276 (9.0%) lymph nodes, which included overt metastasis, micrometastasis and hyalinized cytokeratin particles (HCP). Patients with HCPs in lymph nodes had better outcomes than patients without HCPs in lymph node. A significant prognostic difference between the patients with HCPs and without HCPs was observed in a subgroup of patients with nodal metastasis.
CONCLUSIONS: Our findings suggest that HCP might reflect a degenerative change of cancer cells in lymph nodes and can predict the response to neoadjuvant therapy.

Related: Cancer of the Esophagus Esophageal Cancer

Yang P, Tuo L, Wu Q, Cao X
Licochalcone-A sensitizes human esophageal carcinoma cells to TRAIL-mediated apoptosis by proteasomal degradation of XIAP.
Hepatogastroenterology. 2014 Jul-Aug; 61(133):1229-34 [PubMed] Related Publications
BACKGROUND/AIMS: Esophageal carcinoma is one of the most aggressive human cancers, and novel treatment modality is required. Although expressing adequate levels of functional tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) receptors DR4/DR5, significant proportion of esophageal cancer cells exhibit resistance to the cytotoxic effect of this ligand. Licochalcone-A (LA), a flavonoid present in a variety of edible plants, exhibits a wide spectrum of pharmacologic properties such as anticancer, antioxidant, and anti-inflammatory activities.
METHODOLOGY: Eca109 and TE1 cells were cultured and transfected, then their viability was detected using MTT assay. Immunoprecipitation and immunoblotting analysis and RT-PCR analysis were also performed.
RESULTS: In this study, we found that LA synergistically caused the TRAIL-induced apoptosis in Eca109 and TE1 cells. Such potentiation was achieved through inhibiting Akt activation and promoting proteasomal degradation of X-linked Inhibitor of Apoptosis Protein (XIAP) which mediated the survival signals and allow the cells to escape from apoptosis in various human cancers.
CONCLUSIONS: The combination of TRAIL and LA might be a novel therapeutic strategy for esophageal carcinoma patients who fail to respond to standard chemotherapy.

Related: Apoptosis Cancer of the Esophagus Esophageal Cancer AKT1 TNFSF10

Rades D, Dziggel L, Bartscht T, Gliemroth J
Predicting overall survival in patients with brain metastases from esophageal cancer.
Anticancer Res. 2014; 34(11):6763-5 [PubMed] Related Publications
AIM: To identify survival predictors and develop a survival score for patients with brain metastases from esophageal cancer.
PATIENTS AND METHODS: In 16 patients, seven factors were analyzed including age, gender, Karnofsky performance score (KPS), time from diagnosis of esophageal cancer to irradiation, number of brain metastases, histology, and presence of extracerebral metastases.
RESULTS: Improved survival was significantly associated with KPS≥80 (p<0.001), the presence of one brain metastasis (p=0.007), and no extra-cerebral metastases (p=0.002). These factors were included in the final score. Factor scores were calculated by dividing 6-month survival rates by 10. Total survival scores represented the sums of factor scores and were 2, 7, 10, 19 or 24 points. Six-month survival rates by score were 0%, 0%, 0%, 67% and 100%, respectively. Two groups were formed, those of patients with 2-10 points and those with 19-24 points; 6-month survival was 0% and 88%, respectively (p<0.001).
CONCLUSION: This new score facilitates the selection of individual therapies for patients with brain metastases from esophageal cancer.

Related: Cancer of the Esophagus Esophageal Cancer

Sesti A, Mayerhoefer M, Weber M, et al.
Relevance of calcitonin cut-off in the follow-up of medullary thyroid carcinoma for conventional imaging and 18-fluorine-fluorodihydroxyphenylalanine PET.
Anticancer Res. 2014; 34(11):6647-54 [PubMed] Related Publications
AIM: The American thyroid association (ATA) recommends that additional imaging procedures supplement cervical ultrasonography (US) in any patient with a basal calcitonin value above 150 pg/ml in the follow-up of medullary thyroid carcinoma (MTC). The aim of the present study was to reaffirm or challenge this cut-off for 18-Fluorine-Fluorodihydroxyphenylalanine positron emission tomography (18F-DOPA PET) and conventional imaging ultrasonography (US), computed tomography (CT), magnetic resonance imaging (MRI)).
MATERIALS AND METHODS: Thirty-nine patients (18 females, 21 males), mean age 62 years, range from 35 to 86, followed-up for MTC were included in the present retrospective study. In our patients 64 18F-DOPA scans, 28 neck US, 28 CT and 8 MRI were performed. For all cases basal calcitonin values were available. Sensitivity and specificity of 18F-DOPA PET and conventional imaging (US, CT, MRI) related to calcitonin values were calculated.
RESULTS: According to the calcitonin cut-off of 150 pg/ml, we found the following sensitivities and specificities: 79% and 80% for 18F-DOPA PET, 75% and 92% for US, 80% and 25% for CT, 50% and 75% for MRI. Taking the level of detectable calcitonin, we calculated the following sensitivities: 52% for 18F-DOPA PET, 46% for US, 79% for CT and 38% for MRI.
CONCLUSION: We cannot confirm the calcitonin cut-off proposed by the ATA for the detection of MTC recurrences and contemporaneously we cannot state that 18F-DOPA PET has a very high sensitivity. For the neck region 18F-DOPA PET and US showed similar results. 18F-DOPA PET/CT seems to be the best imaging modality for whole-body tumor detection. Bone metastases are best detected by MRI.

Related: Thyroid Cancer

Steffen A, Hasselbacher K, Heinrichs S, Wollenberg B
Botulinum toxin for salivary disorders in the treatment of head and neck cancer.
Anticancer Res. 2014; 34(11):6627-32 [PubMed] Related Publications
BACKGROUND/AIM: During the treatment of head and neck cancer (HNC), salivary problems may impair a patient's healing process. Botulinum toxin (BoNT) is accepted as an effective treatment option for reducing salivary flow. We aimed to describe the features of patients treated with BoNT to determine the effects of BoNT.
PATIENTS AND METHODS: Twenty-five patients over a five-year period were retrospectively included. The patients suffered at different stages of oncologic treatment. The cohort primarily had larger primary tumors that required complex oncological treatment.
RESULTS: The condition improved in more than three quarters of the 19 patients with functional hypersalivation. Four of six cases suffering from a salivary fistula demonstrated an obvious reduction in symptoms.
CONCLUSIONS: Injection of BoNT, to temporarily reduce saliva flow, is a safe tool in the treatment of HNC even in situations involving repeated therapy or high dosage. The main clinical side-effect of BoNT is insufficient reduction of the salivary problem.

Zätterström U, Boysen M, Evensen JF
Significance of self-reported symptoms as part of follow-up routines in patients treated for oral squamous cell carcinoma.
Anticancer Res. 2014; 34(11):6593-9 [PubMed] Related Publications
BACKGROUND: There is little evidence to prove that frequent out-patient consultations lead to better prognosis in patients treated for oral squamous cell carcinoma. Furthermore, there is no consensus regarding the timing and number of follow-up consultations or the duration of monitoring after completed therapy.
MATERIALS AND METHODS: We prospectively recorded demographic and clinical data of 537 patients treated over a period of 15 years with complete follow-up of 18 years in a tertiary academic Center.
RESULTS: Out of 537 patients considered free of disease after treatment, 196 (36%) developed recurrent disease during follow-up. Self-reported symptoms led to diagnosis of the recurrence in 78% of the cases. Only 22% of recurrences were detected through physical examination of asymptomatic patients. There was no difference in disease-free survival in-between these two groups.
CONCLUSION: Follow-up routines are indispensable as part of cancer treatment but can be more cost-efficient when patients are educated and encouraged to report subjective symptoms. Trained personnel in collaboration with head and neck specialists can handle parts of follow-up routines.

Related: Oral Cancer

Aljammaz I, Al-Otaibi B, Al-Hokbany N, et al.
Development and pre-clinical evaluation of new 68Ga-NOTA-folate conjugates for PET imaging of folate receptor-positive tumors.
Anticancer Res. 2014; 34(11):6547-56 [PubMed] Related Publications
In an attempt to develop new folate radiotracers with favorable biochemical properties for detecting folate receptor-positive cancers, we synthesized 68Ga-NOTA- and 68Ga-NOTAM-folate conjugates using a straightforward and a one-step simple reaction. Radiochemical yields were greater than 95% (decay-corrected) with total synthesis time of less than 20 min. Radiochemical purities were always greater than 98% without high-performance liquid chromatography (HPLC) purification. These synthetic approaches hold considerable promise as a rapid and simple method for 68Ga-folate conjugate preparation with high radiochemical yield in a short synthesis time. In vitro tests on the KB cell line showed that significant amounts of the radioconjugates were associated with cell fractions. Biodistribution studies in nude mice bearing human KB xenografts, demonstrated a significant tumor uptake and favorable biodistribution profile for 68Ga-NOTA-folate over the 68Ga-NOTAM-folate conjugate. The uptake in the tumors was blocked by excess injection of folic acid, suggesting a receptor-mediated process. These results demonstrate that the 68Ga-NOTA-folate conjugate may be useful as a molecular probe for detection and staging of folate receptor-positive cancers, such as ovarian cancer and their metastasis, as well as monitoring tumor response to treatment.

Related: Apoptosis Oral Cancer

Krikelis D, Kotoula V, Bobos M, et al.
Protein and mRNA expression of notch pathway components in operable tumors of patients with laryngeal cancer.
Anticancer Res. 2014; 34(11):6495-503 [PubMed] Related Publications
BACKGROUND: There exist substantial evidence that laryngeal cancer represents a unique entity among squamous head and neck carcinomas.
MATERIALS AND METHODS: Tumors from 289 patients with squamous cell laryngeal cancer were assessed for protein (immunohistochemistry) and mRNA (qRT-PCR) expression of Notch pathway components (Notch1 to 4 receptors and Jagged1 ligand) on tissue microarrays.
RESULTS: In univariate analysis, enhanced nuclear Jagged1 expression conferred a longer disease-free survival (DFS) (p=0.013) and overall survival (OS) (p=0.004), in contrast to the unfavorable prognostic value of Notch3 for both DFS (p=0.009) and OS (p=0.024). In multivariate analysis, overexpression of either Notch or cytoplasmic Jagged1 conferred an unfavorable effect on DFS (Hazard Ratio=1.88, 95% Confidence Interval=1.03-3.43, p=0.04).
CONCLUSION: Our study indicates a consistent unfavorable effect of Notch3 and cytoplasmic Jagged1 protein expression, a favorable impact of nuclear Jagged 1 localization, and a differential prognostic value of Notch2 expression according to the presence of cytoplasmic Jagged 1.

Related: Cancer of the Larynx Laryngeal Cancer - Molecular Biology

Jarząb A, Grabarska A, Kiełbus M, et al.
Osthole induces apoptosis, suppresses cell-cycle progression and proliferation of cancer cells.
Anticancer Res. 2014; 34(11):6473-80 [PubMed] Related Publications
BACKGROUND: The aim of the present study was to determine the effects of osthole on cell proliferation and viability, cell-cycle progression and induction of apoptosis in human laryngeal cancer RK33 and human medulloblastoma TE671 cell lines.
MATERIALS AND METHODS: Cell viability was measured by means of the MTT method and cell proliferation by the 5-bromo-2-deoxyuridine (BrdU) incorporation assay. Cell-cycle progression was determined by flow cytometry, and induction of apoptosis by release of oligonucleosomes to the cytosol. The gene expression was estimated by a quantitative polymerase chain reaction (qPCR) method. High-performance counter-current chromatography (HPCCC) was applied for isolation of osthole from fruits of Mutellina purpurea.
RESULTS: Osthole decreased proliferation and cell viability of cancer cells in a dose-dependent manner. The tested compound induced apoptosis, increased the cell numbers in G1 and decreased cell number in S/G2 phases of the cell cycle, differentially regulating CDKN1A and TP53 gene expression depending on cancer cell type.
CONCLUSION: Osthole could be considered as a potential compound for cancer therapy and chemoprevention.

Related: Apoptosis CDKN1A Cancer of the Larynx Laryngeal Cancer - Molecular Biology Childhood Medulloblastoma / PNET TP53

Kida-Takaoka S, Yamaai T, Mizukawa N, et al.
Surrounding cells affect the gene expression pattern of human beta-defensins in squamous cell carcinoma in vitro.
Anticancer Res. 2014; 34(11):6443-9 [PubMed] Related Publications
BACKGROUND/AIM: Defensins are basic peptides involved in non-immune bio-defense mechanisms in a normal epithelium. Human oral squamous cell carcinoma cells (OSCC) also produce human beta-defensins (HBDs), although their exact function is not clear. This study aimed to analyze the variation in gene expression levels of hBDs in co-cultures of OSCC with murine cells.
MATERIALS AND METHODS: Two OSCC cell lines (HSC-3, HSC-4) were co-cultured with mouse embryonic fibroblasts, NIH/3T3 or a mouse chondrogenic cell line derived from teratocarcinoma, ATDC5, for 1.5 days. Expression patterns of the hBD genes were investigated by real-time polymerase chain reaction (RT-PCR).
RESULTS: hBD1 expression increased when co-cultured with NIH/3T3 but decreased when co-cultured with ATDC5. Expression of hBD2 and hBD4 tended to decrease. OSCC cells formed colonies when co-cultured with NIH/3T3 but were scattered when co-cultured with ATDC5.
CONCLUSION: hBDs expression in OSCC is dependent on the type of co-cultured cells and differences in gene expression may be responsible for the morphological differences observed. OSCC may produce HBDs for purposes other than bio-defense by surrounding cells.

Related: Apoptosis Oral Cancer Testicular Cancer

Park YJ, Kim EK, Moon S, et al.
Human telomerase reverse transcriptase is a promising target for cancer inhibition in squamous cell carcinomas.
Anticancer Res. 2014; 34(11):6389-95 [PubMed] Related Publications
BACKGROUND/AIM: The present study aimed to investigate whether the down-regulation of human telomerase reverse transcriptase (hTERT) may induce an anti-invasive effect in oral squamous cell cancer cell lines.
MATERIALS AND METHODS: A genetically-engineered squamous carcinoma cell line overexpressing hTERT in immortalized oral keratinocytes transfected by human papilloma virus (HPV)-16 E6/E7 (IHOK) was used. In vivo tumorigenicity was examined using an orthotopic xenograft model of nude mice. For evaluating anti-invasive activity by knockdown of hTERT expression, transwell invasion assay and real-time polymerase chain reaction (PCR) for matrix metalloproteinases (MMP) were employed.
RESULTS: The down-regulation of hTERT expression reduced the invasive activity and MMP expression. This result was re-confirmed in the HSC3 oral squamous carcinoma cell line.
CONCLUSION: Targeting hTERT may lead to novel therapeutic approaches.

Related: CDK4 Oral Cancer TERT

Sørensen BS, Busk M, Horsman MR, et al.
Effect of radiation on cell proliferation and tumor hypoxia in HPV-positive head and neck cancer in vivo models.
Anticancer Res. 2014; 34(11):6297-304 [PubMed] Related Publications
BACKGROUND/AIM: Human papilloma virus-associated head and neck squamous cell carcinomas (HNSCC) represent a distinct subgroup of HNSCC characterized by a favorable prognosis and a distinct molecular biology. There is a range of unresolved questions regarding the different biology and clinical outcome of HPV-positive HNSCC. The purpose of the present project was to obtain insight into the biology of treatment responsiveness of HPV-related HNSCC.
MATERIALS AND METHODS: Tumor xenografts were established from HPV-negative (FaDuDD,) and HPV-positive (UD2 and UMSCC47) HNSCC cell lines. Tumors were treated with 10 Gy or 20 Gy and the effect on the tumor microenvironment was studied at different time points after treatment. Cryosections were imaged for cell proliferation, hypoxia, vessel density and vessel perfusion.
RESULTS: In the HPV-positive tumor models the levels of cell proliferation decreased significantly following irradiation. This was not seen in the HPV-negative model (FaDuDD). Furthermore, it was found that the tumor hypoxic fraction decreased over time after treatment in irradiated HPV-positive tumors and not in the HPV-negative tumors.
CONCLUSION: The radiosensitivity previously observed in vitro could be applied in vivo in respect to a radiation-induced decrease in proliferating cells. A decreasing hypoxic fraction following irradiation in the HPV-positive tumors could explain the lack of benefit from hypoxic modifiers observed in patients.

Related: Apoptosis

Dai Y, Li C, Xie Y, et al.
Interventions for dysphagia in oesophageal cancer.
Cochrane Database Syst Rev. 2014; 10:CD005048 [PubMed] Related Publications
BACKGROUND: Most patients with oesophageal and gastro-oesophageal carcinoma are diagnosed at an advanced stage and require palliative intervention. Although there are many kinds of interventions, the optimal one for the palliation of dysphagia remains unclear. This review updates the previous version published in 2009.
OBJECTIVES: The aim of this review was to systematically analyse and summarise the efficacy of different interventions used in the palliation of dysphagia in primary oesophageal and gastro-oesophageal carcinoma.
SEARCH METHODS: To find new studies for this updated review, in January 2014 we searched, according to the Cochrane Upper Gastrointestinal and Pancreatic Diseases model, the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library), MEDLINE, EMBASE and CINAHL; and major conference proceedings (up to January 2014).
SELECTION CRITERIA: Only randomised controlled trials (RCTs) were included in which patients with inoperable or unresectable primary oesophageal cancer underwent palliative treatment. Different interventions like rigid plastic intubation, self-expanding metallic stent (SEMS) insertion, brachytherapy, external beam radiotherapy, chemotherapy, oesophageal bypass surgery, chemical and thermal ablation therapy, either head-to-head or in combination, were included. The primary outcome was dysphagia improvement. Secondary outcomes included recurrent dysphagia, technical success, procedure related mortality, 30-day mortality, adverse effects and quality of life.
DATA COLLECTION AND ANALYSIS: Data collection and analysis were performed in accordance with the methods of the Cochrane Upper Gastrointestinal and Pancreatic Diseases Review Group.
MAIN RESULTS: We included 3684 patients from 53 studies. SEMS insertion was safer and more effective than plastic tube insertion. Thermal and chemical ablative therapy provided comparable dysphagia palliation but had an increased requirement for re-interventions and for adverse effects. Anti-reflux stents provided comparable dysphagia palliation to conventional metal stents. Some anti-reflux stents might have reduced gastro-oesophageal reflux and complications. Newly-designed double-layered nitinol (Niti-S) stents were preferable due to longer survival time and fewer complications compared to simple Niti-S stents. Brachytherapy might be a suitable alternative to SEMS in providing a survival advantage and possibly a better quality of life, and might provide better results when combined with argon plasma coagulation or external beam radiation therapy.
AUTHORS' CONCLUSIONS: Self-expanding metal stent insertion is safe, effective and quicker in palliating dysphagia compared to other modalities. However, high-dose intraluminal brachytherapy is a suitable alternative and might provide additional survival benefit with a better quality of life. Some anti-reflux stents and newly-designed stents lead to longer survival and fewer complications compared to conventional stents. Combinations of brachytherapy with self-expanding metal stent insertion or radiotherapy are preferable due to the reduced requirement for re-interventions. Rigid plastic tube insertion, dilatation alone or in combination with other modalities, and chemotherapy alone are not recommended for palliation of dysphagia due to a high incidence of delayed complications and recurrent dysphagia.

Related: Brachytherapy Cancer of the Esophagus Esophageal Cancer

Elliott JA, O'Farrell NJ, King S, et al.
Value of CT-PET after neoadjuvant chemoradiation in the prediction of histological tumour regression, nodal status and survival in oesophageal adenocarcinoma.
Br J Surg. 2014; 101(13):1702-11 [PubMed] Related Publications
BACKGROUND: The role of CT-PET after neoadjuvant chemoradiation (nCRT) for prediction of pathological response and oncological outcome in oesophageal and junctional adenocarcinoma (OAC) is unclear. The relationship between complete metabolic response (cMR), pathological complete response (pCR) and nodal status has not been clarified.
METHODS: Patients with locally advanced OAC selected to receive nCRT and surgery with curative intent, on the basis of staging that included CT-PET positivity, were included. Repeat scanning (PET2) with an identical protocol was performed 2-4 weeks after completion of nCRT (cisplatin and 5-fluorouracil plus 44 Gy radiation). Changes in [(18) F]fluorodeoxyglucose uptake, considered as either a maximum standardized uptake value (SUVmax) or a relative reduction (%ΔSUVmax), and PET-predicted nodal status following nCRT were compared with histopathological response, histological node positivity and survival.
RESULTS: One hundred consecutive patients with PET-positive OAC were studied. Following nCRT, PET2 identified M1 disease in 2·0 per cent of patients. There were no significant associations between PET2 SUVmax or %ΔSUVmax with respect to primary tumour stage (ypT) (P = 0.216 and P = 0·975 respectively), tumour regression grade (P = 0·109 and P = 0·232), pCR (P = 0·633 and P = 0·870) or complete resection (R0) (P = 0·440 and P = 0·235). The sensitivity of PET2 for ypN was 10 per cent. %ΔSUVmax was not associated with disease-free or overall survival (P = 0·162 and P = 0·154 respectively). Of 46 patients with a cMR on PET2, 37 (80 per cent) had histological evidence of residual tumour in the resected specimen, and cMR was not associated with overall survival benefit (P = 0·478).
CONCLUSION: CT-PET following nCRT for OAC has poor prognostic and discriminatory value for clinical application.

Related: Cancer of the Esophagus Esophageal Cancer

Hilly O, Stern-Shavit S, Iran S, Feinmesser R
Treatment decisions and adherence to guidelines in the treatment of low risk papillary carcinoma of the thyroid.
Isr Med Assoc J. 2014; 16(9):548-52 [PubMed] Related Publications
BACKGROUND: Treatment guidelines for well-differentiated papillary thyroid carcinoma (PTC) are based on retrospective studies and vary among professional thyroid associations.
OBJECTIVES: To evaluate physician adherence to guidelines, overall and by specialty.
METHODS: Questionnaires on the approach to low risk PTC were distributed among 51 surgeons and endocrinologists treating patients with PTC in tertiary medical centers.
RESULTS: A wide range of answers was recorded among physicians regarding the danger posed by low risk PTC to the patient's life, urgency with which treatment should be administered, type of treatment, and risks associated with this treatment. There was a significant between-group difference in treatment preference: endocrinologists chose total thyroidectomy with radioactive iodine, while surgeons favored hemithyroidectomy alone.
CONCLUSIONS: There is a wide difference in treatment recommendations between treating physicians and different specialties with regard to low risk PTC. The wide variation within and between soecialties may be explained by biases.

Related: Thyroid Cancer

Marom T, Segal D, Erlich T, et al.
Ethical and clinical dilemmas in patients with head and neck tumors visiting a field hospital in the Philippines.
Am J Disaster Med. 2014; 9(3):211-9 [PubMed] Related Publications
OBJECTIVE: To describe clinical and ethical dilemmas in patients presenting with head and neck (H&N) tumors to a field hospital in the "subacute" period following a typhoon.
METHODS: We retrospectively reviewed charts of H&N patients presenting to an integrated Israeli-Filipino medical facility, which was operated more than 11 days.
RESULTS: Of the 1,844 adult patients examined, 85 (5 percent) presented with H&N tumors. Of those, 70 (82 percent) were females, with a mean age of 43 ± 15 years. Thyroid neoplasms were the most common tumors (68, 80 percent). Despite limited resources, we contributed to the workup and treatment of several patients. To better illustrate our dilemmas, we present four key patients, in whom we favored diagnostic/therapeutic interventions in two, and opted to defer any intervention in two.
CONCLUSIONS: In a relief mission, despite the lack of clinical and pathological staging and questionable continuity of care, surgical interventions can be considered for therapeutic, palliative, and diagnostic purposes.

Aliabadi-Wahle S, Kelly TL, Rozenfeld Y, et al.
Treatment strategies for primary hyperparathyroidism: what is the cost?
Am Surg. 2014; 80(11):1146-51 [PubMed] Related Publications
Primary hyperparathyroidism (HPT) contributes to the onset of many chronic conditions. Although parathyroidectomy is the only definitive treatment, observation remains a valid option. Over a 3-year span, a major health plan was queried for HPT and benign parathyroid neoplasm. Patients with secondary and tertiary HPT, Stage III to V kidney disease, and prior renal transplant were excluded. Patients were divided into: observation (Group 1), parathyroidectomy during the study period (Group 2), and parathyroidectomy before the study group (Group 3), and were compared with a control group of 27,092 adult members without HPT using analysis of variance. The 3-year mean total allowed expenditure for Group One (n = 559), Group Two (n = 93), and Group Three (n = 48) were $21,267, $37,043, and $14,702, respectively. Groups One and Two had significantly higher use than the nonparathyroid group (P < 0.0001), whereas that of Group Three was comparable. Group Two had the highest cost, whereas Group Three had a significantly lower cost than Group One (P 0.0001). Primary hyperparathyroidism is associated with a higher use of healthcare resources. Patients observed incurred a higher allowed expenditure than those with prior parathyroidectomy. Surgical treatment may represent a cost-effective strategy for treatment of hyperparathyroidism, although more comprehensive studies are needed to confirm these findings.

Related: Parathyroid Cancer

Zhao Q, Pizer S, Niethammer M, Rosenman J
Geometric-feature-based spectral graph matching in pharyngeal surface registration.
Med Image Comput Comput Assist Interv. 2014; 17(Pt 1):259-66 [PubMed] Related Publications
Fusion between an endoscopic movie and a CT can aid specifying the tumor target volume for radiotherapy. That requires a deformable pharyngeal surface registration between a 3D endoscope reconstruction and a CT segmentation. In this paper, we propose to use local geometric features for deriving a set of initial correspondences between two surfaces, with which an association graph can be constructed for registration by spectral graph matching. We also define a new similarity measurement to provide a meaningful way for computing inter-surface affinities in the association graph. Our registration method can deal with large non-rigid anatomical deformation, as well as missing data and topology change. We tested the robustness of our method with synthetic deformations and showed registration results on real data.

Licci S, Puma F, Sbaraglia M, Ascani S
Primary intrathymic lymphangioma.
Am J Clin Pathol. 2014; 142(5):683-8 [PubMed] Related Publications
OBJECTIVES: Lymphangiomas are relatively uncommon lesions of the lymphatic channels that can arise in virtually any part of the body provided by lymphatic vessels. The most common localization is the head/neck region, with only sporadic reports in other sites. The mediastinum is a rare location, with around 20 cases reported in the literature.
METHODS: We describe one case of mediastinal lymphangioma with a true intrathymic localization, which to our knowledge has never been described.
RESULTS: The gross features and microscopic findings are reported with a discussion of the clinicopathologic signatures of this pathologic entity.
CONCLUSIONS: Intrathymic lymphangioma should always be taken into consideration in the differential diagnosis of cystic mediastinal lesions in children and adult patients.

Jacobs M, Henselmans I, Macefield RC, et al.
Delphi survey to identify topics to be addressed at the initial follow-up consultation after oesophageal cancer surgery.
Br J Surg. 2014; 101(13):1692-701 [PubMed] Related Publications
BACKGROUND: There is no consensus among patients and healthcare professionals (HCPs) on the topics that need to be addressed after oesophageal cancer surgery. The aim of this study was to identify these topics, using a two-round Delphi survey.
METHODS: In round 1, patients and HCPs (surgeons, dieticians, nurses) were invited to rate the importance of 49 topics. The proportion of panellists that considered a topic to be of low, moderate or high importance was then calculated for each of these two groups. Based on these proportions and the i.q.r., topics were categorized as: 'consensus to be included', 'consensus to be excluded' and 'no consensus'. Only topics in the first category were included in the second round. In round 2, panellists were provided with individual and group feedback. To be included in the final list, topics had to meet criteria for consensus and stability.
RESULTS: There were 108 patients and 77 HCPs in the round 2 analyses. In general, patients and HCPs considered the same topics important. The final list included 23 topics and revealed that it was most important to address: cancer removed/lymph nodes, the new oesophagus, eating and drinking, surgery, alarming new complaints and the recovery period.
CONCLUSION: The study provides surgeons with a list of topics selected by patients and HCPs that may be addressed systematically at the initial follow-up consultation after oesophageal cancer surgery.

Related: Cancer of the Esophagus Esophageal Cancer

Melchers LJ, Clausen MJ, Mastik MF, et al.
Head and neck squamous cell carcinomas do not express EGFRvIII.
Int J Radiat Oncol Biol Phys. 2014; 90(2):454-62 [PubMed] Related Publications
PURPOSE: To assess the prevalence of EGFRvIII, a specific variant of EGFR (epidermal growth factor receptor), in 3 well-defined cohorts of head and neck squamous cell carcinoma (HNSCC).
METHODS AND MATERIALS: Immunohistochemistry for the specific detection of EGFRvIII using the L8A4 antibody was optimized on formalin-fixed, paraffin-embedded tissue using glioblastoma tissue. It was compared with EGFR and EGFRvIII RNA expression using a specific reverse transcription-polymerase chain reaction also optimized for formalin-fixed, paraffin-embedded tissue. Tissue microarrays including 531 HNSCCs of various stages with complete clinicopathologic and follow-up data were tested for the presence of EGFRvIII.
RESULTS: None of the 531 cases showed EGFRvIII protein expression. Using an immunohistochemistry protocol reported by others revealed cytoplasmic staining in 8% of cases. Reverse transcription-polymerase chain reaction for the EGFRvIII transcript of the 28 highest cytoplasmic staining cases, as well as 69 negative cases, did not show expression in any of the tested cases, suggesting aspecific staining by a nonoptimal protocol.
CONCLUSIONS: The EGFRvIII mutation is not present in HNSCC. Therefore, EGFRvIII does not influence treatment response in HNSCC and is not a usable clinical prognostic marker.

Warren S, Partridge M, Carrington R, et al.
Radiobiological determination of dose escalation and normal tissue toxicity in definitive chemoradiation therapy for esophageal cancer.
Int J Radiat Oncol Biol Phys. 2014; 90(2):423-9 [PubMed] Free Access to Full Article Related Publications
PURPOSE: This study investigated the trade-off in tumor coverage and organ-at-risk sparing when applying dose escalation for concurrent chemoradiation therapy (CRT) of mid-esophageal cancer, using radiobiological modeling to estimate local control and normal tissue toxicity.
METHODS AND MATERIALS: Twenty-one patients with mid-esophageal cancer were selected from the SCOPE1 database (International Standard Randomised Controlled Trials number 47718479), with a mean planning target volume (PTV) of 327 cm(3). A boost volume, PTV2 (GTV + 0.5 cm margin), was created. Radiobiological modeling of tumor control probability (TCP) estimated the dose required for a clinically significant (+20%) increase in local control as 62.5 Gy/25 fractions. A RapidArc (RA) plan with a simultaneously integrated boost (SIB) to PTV2 (RA62.5) was compared to a standard dose plan of 50 Gy/25 fractions (RA50). Dose-volume metrics and estimates of normal tissue complication probability (NTCP) for heart and lungs were compared.
RESULTS: Clinically acceptable dose escalation was feasible for 16 of 21 patients, with significant gains (>18%) in tumor control from 38.2% (RA50) to 56.3% (RA62.5), and only a small increase in predicted toxicity: median heart NTCP 4.4% (RA50) versus 5.6% (RA62.5) P<.001 and median lung NTCP 6.5% (RA50) versus 7.5% (RA62.5) P<.001.
CONCLUSIONS: Dose escalation to the GTV to improve local control is possible when overlap between PTV and organ-at-risk (<8% heart volume and <2.5% lung volume overlap for this study) generates only negligible increase in lung or heart toxicity. These predictions from radiobiological modeling should be tested in future clinical trials.

Related: Cancer of the Esophagus Esophageal Cancer

Aaltonen LM, Rautiainen N, Sellman J, et al.
Voice quality after treatment of early vocal cord cancer: a randomized trial comparing laser surgery with radiation therapy.
Int J Radiat Oncol Biol Phys. 2014; 90(2):255-60 [PubMed] Related Publications
OBJECTIVE: Early laryngeal cancer is usually treated with either transoral laser surgery or radiation therapy. The quality of voice achieved with these treatments has not been compared in a randomized trial.
METHODS AND MATERIALS: Male patients with carcinoma limited to 1 mobile vocal cord (T1aN0M0) were randomly assigned to receive either laser surgery (n=32) or external beam radiation therapy (n=28). Surgery consisted of tumor excision with a CO2 laser with the patient under general anaesthesia. External beam radiation therapy to the larynx was delivered to a cumulative dose of 66 Gy in 2-Gy daily fractions over 6.5 weeks. Voice quality was assessed at baseline and 6 and 24 months after treatment. The main outcome measures were expert-rated voice quality on a grade, roughness, breathiness, asthenia, and strain (GRBAS) scale, videolaryngostroboscopic findings, and the patients' self-rated voice quality and its impact on activities of daily living.
RESULTS: Overall voice quality between the groups was rated similar, but voice was more breathy and the glottal gap was wider in patients treated with laser surgery than in those who received radiation therapy. Patients treated with radiation therapy reported less hoarseness-related inconvenience in daily living 2 years after treatment. Three patients in each group had local cancer recurrence within 2 years from randomization.
CONCLUSIONS: Radiation therapy may be the treatment of choice for patients whose requirements for voice quality are demanding. Overall voice quality was similar in both treatment groups, however, indicating a need for careful consideration of patient-related factors in the choice of a treatment option.

Related: Cancer of the Larynx Laryngeal Cancer - Molecular Biology

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